Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender

Abstract

In conditions of ischemia/reperfusion (I/R), the relative use of all available substrates by the heart has a significant effect on the recovery of the organ. This substrate preference in perfused hearts is influenced by ischemia. We followed the metabolic fate of [U-(13) C]glucose and [3-(13) C]lactate in hearts preserved in Celsior (Cs) and histidine buffer solution (HBS) for 4 or 6 h and subsequently perfused with a Krebs-Henseleit solution (KH) containing [U-(13) C]glucose and [3-(13) C]lactate. We also assessed gender-specific metabolic modulation in our I/R experimental conditions. Hearts from male and female Wistar rats (6-8 weeks) were subjected to moderate (0-240 min) or prolonged (240-360 min) cold ischemia whilst immersed in Cs and HBS, and perfused for 30 min with KH containing [U-(13) C]glucose and [3-(13) C]lactate. After perfusion, hearts were freeze-clamped and metabolites were extracted for (13) C NMR isotopomer analysis. In control conditions, there were no differences with regard to lactate origin in hearts from males and females. After 6 h of preservation in Cs, lactate origin was mostly from [U-(13) C]glucose in hearts from males and from [3-(13) C]lactate in hearts from females. During the 6 h of organ preservation in HBS, the lactate pool showed a strong contribution from unenriched sources in male hearts and from [U-(13) C]glucose in female hearts. The glutamate C2/C4 ratio was stable or increased in hearts from females after I/R, and the alanine index increased in hearts from both males and females. Octanoate was, as predicted, the preferential substrate during perfusion. Glucose and lactate suffer a distinct metabolic fate in our I/R conditions, which is related to the cardioplegic solution used during organ storage, and the gender. Hearts from females appear to be less sensitive to I/R injury, and heart preservation in HBS proved to be effective in enhancing anaplerosis during perfusion, especially in hearts from females.

Improved renal ischemia tolerance in females influences kidney transplantation outcomes

“…The ability to administer β-estradiol or any medication to reduce renal IRI in a transplantation setting depends on the persistence of its beneficial effects or, at a minimum, the lack of detrimental effects in the procurement of other organs. Sex differences in IRI tolerance are well described in cardiac tissue (7,31,32) and the nervous system (8,33), and short-term administration of 17β-estradiol directly improved IRI tolerance in rat livers (9) and myocardium (34) when given 1 and 3 hours before injury, respectively, making nonrenal off-target effects of lesser concern.…”

“…Sexual dimorphism with respect to tolerance of IRI has been noted in a number of laboratory animal models (7)(8)(9)(10)(11). Generally, there is consensus that female sex conveys greater tolerance of, or protection from, IRI relative to the male sex.…”

Dehydroepiandrosterone and 7-oxo-dehydroepiandrosterone in male reproductive health: Implications of differential regulation of human Sertoli cells metabolic profile

“…Proton nuclear magnetic resonance ( 1 H NMR) 1 H NMR spectra were acquired as previously described [30]. Sodium fumarate (final concentration of 1 mM) was used as an internal reference (6.50 ppm) to quantify the following metabolites present in the extracellular media of hSCs (multiplet, ppm): lactate (doublet, 1.33); alanine (doublet, 1.45), acetate (singlet, 1.90), pyruvate (singlet, 2.35), citrate (multiplet, 2.57-2.72) and H1-a-glucose (doublet, 5.22).…”

White tea consumption improves cardiac glycolytic and oxidative profile of prediabetic rats

“…To satisfy its high-energy requirements, the cardiac muscle is capable of consuming several substrates, but glucose plays a key role, particularly when the heart is subjected to unfavourable conditions (Alves, Oliveira, & Carvalho, 2011). Among the several metabolic alterations induced by hyperglycaemia, it has been reported that the myocardium accelerates glycolysis, producing high levels of lactate, and this may be a contributing factor for the cardiac dysfunction associated with DM.…”